Non-Small Cell Lung Cancer
Conditions
Brief summary
The purposes of this study are to determine: The safety of enzastaurin plus pemetrexed with carboplatin, pemetrexed with carboplatin, or docetaxel with carboplatin and any side effects that might be associated with the combination of these drugs. Whether the combination of enzastaurin plus pemetrexed and carboplatin or pemetrexed and carboplatin can help participants with non-small cell lung cancer (NSCLC) live longer, compared with the combination of docetaxel and carboplatin. Whether the combination of enzastaurin plus pemetrexed and carboplatin or pemetrexed and carboplatin can make your tumor smaller or disappear, and for how long, compared with the combination of docetaxel and carboplatin. The effects of enzastaurin plus pemetrexed with carboplatin, pemetrexed with carboplatin or docetaxel with carboplatin have on your disease related symptoms. The relation of smoking history and hormone replacement therapy (for women only) may have to your lung cancer treatment results. The effects of certain genes and proteins in samples of your blood and tumor tissue in order to learn more about NSCLC and how enzastaurin works in the body.
Interventions
DRUGpemetrexed
500 milligrams per square meter (mg/m\^2), intravenous (IV), once every (q) 21 days, six 21 day cycles or progressive disease
DRUGdocetaxel
75 mg/m\^2, IV, q 21 days, six 21 day cycles or progressive disease
DRUGcarboplatin
Area under the curve (AUC) 6, IV, q 21 days, six 21 day cycles or progressive disease
DRUGenzastaurin
1125-1200 milligrams (mg) loading dose then 500 mg, oral, daily, until disease progression
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* You must have been diagnosed with NSCLC. * You must be able to visit the doctor's office weekly during the active treatment period and as needed during the study follow-up period. * You must be willing and able to swallow capsules. * Your entry labs and medical tests must meet study requirements. * You must be willing to have blood samples drawn and tissue samples obtained for gene and protein testing.
Exclusion criteria
* You have received radiation within 2 weeks of study enrollment. * You have previously received any anti-cancer drug therapy for NSCLC. * You have an active infection or other serious condition. * You take aspirin or aspirin-like medication regularly and are not able to stop taking them for a few days during each cycle of chemotherapy. * You have recently lost a significant amount of weight.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Disease Progression | Baseline to measured PD up to 22.3 months | Time to disease progression was defined as the time from randomization to the first date of documented disease progression or death if the participant dies due to disease progression. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. Progressive disease (PD) was defined as having at least a 20% increase in sum of the longest diameter of target lesions. For participants who have not had documented disease progression, time to disease progression was censored at the date of death or date of last visit. For participants who received other anti-tumor therapy prior to disease progression, time to disease progression was censored at the first available date of other anti-tumor therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of Smoking History (All Participants) and Hormone Replacement Therapy (Female Participants Only) Associated With Clinical Outcomes | Baseline | Data for smoking history and hormone replacement therapy were collected but were not intended to be analyzed at the individual study level. |
| Number of Participants With Adverse Events (AEs) or Deaths | Baseline through study completion up to 6 cycles (21-day cycle each) and 30-day safety follow-up | Data presented are the number of participants who experienced 1 or more AEs or any serious AEs (SAEs) regardless of causality, or deaths during the study including 30 days after treatment discontinuation. A summary of SAEs and other non-serious AEs is located in the Reported Adverse Events section of this report. |
| Change From Baseline in Total Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale | Baseline, Cycle 1 (Week 3), Cycle 2 (Week 6), Cycle 3 (Week 9), Cycle 4 (Week 12), Cycle 5 (Week 15) and Cycle 6 (Week 18) [21-day cycle each] | The FACT-L version 4 scale is used to assess health-related quality of life (HRQoL) in participants with lung cancer. The FACT-L has 5 subscales: Physical Well-Being (PWB), Social and Family Well-Being (SFWB) and Functional Well-Being (FWB) subscales which include 7 items each, Emotional Well-Being (EWB) subscale which includes 6 items, and a Lung-Cancer Specific (LCS) subscale which include 7 items. Total FACT-L is the sum of all 5 subscales. Each item is scored from 0 to 4 giving a total overall score from 0 equal to worst quality of life to 136 equal to best quality of life. The Least Square (LS) mean was calculated using an analysis of covariance (ANCOVA) model adjusted for change scores and baseline scores. |
| Change From Baseline in Total Functional Assessment of Cancer Therapy -Taxane (FACT-Taxane) Scale | Baseline, Cycle 1 (Week 3), Cycle 2 (Week 6), Cycle 3 (Week 9), Cycle 4 (Week 12), Cycle 5 (Week 15) and Cycle 6 (Week 18) [21-day cycle each] | The FACT-Taxane version 4 scale is used to assess HRQoL in participants receiving taxane chemotherapy. The FACT-taxane has 5 subscales: PWB, SFWB, and FWB subscales which include 7 items each, EWB subscale which includes 6 items, and a taxane subscale which include 16 items and has two domains (neurotoxicity and taxane). Total FACT-Taxane is the sum of all the 5 subscales. Each item is scored from 0 to 4 giving a total overall score from 0 worst quality of life to 172 best quality of life. The LS mean was calculated using an ANCOVA model adjusted for change scores and baseline scores. |
| Tumor Biomarkers Associated With Clinical Outcomes | Baseline, Cycle 1, Cycle 2 (21-day cycle each), and 30-day post study treatment follow-up | As specified in the protocol, tumor biomarker samples were collected from participants on the pemetrexed arms only but were not intended to be analyzed at the individual study level. |
| Number of Participants With Complete Response (CR) or Partial Response (PR) [Tumor Response] | Baseline to measured PD up to 22.3 months | Response was defined using RECIST, version 1.0 criteria. Participants with a best response of CR or PR were considered to have had a tumor response. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions. |
| Duration of CR or PR (Duration of Response) | Date of first response to the date of progression or death due to any cause up to 22.3 months | The duration of a CR or PR was defined as the time from first objective status assessment of CR or PR to the first time of progression or death due to any cause. Response was defined using RECIST, version 1.0 criteria. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions. |
| Time-to-Treatment Failure (TTF) | Baseline to stopping treatment up to 14.1 months | TTF was defined as the time from randomization to the first observation of PD, death due to any cause, or early discontinuation of treatment. Response was defined using RECIST, version 1.0 criteria. PD was defined as having at least a 20% increase in sum of longest diameter of target lesions. TTF was censored at the date of the last follow-up visit for participants who did not discontinue early, who were still alive, and who have not progressed. |
| Overall Survival (OS) | Baseline to date of death from any cause up to 35 months | OS was the duration from the date of randomization to the date of death from any cause. For participants who were alive, OS was censored at the date of last follow-up visit or at the date of last contact. |
Countries
United States
Participant flow
Pre-assignment details
Presented in the participant flow are the reasons participants discontinued from study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Enzastaurin/Pemetrexed/Carboplatin Enzastaurin loading dose of 1125 mg or 1200 mg orally on Day -7 (pre-chemotherapy) followed by 500 mg administered orally once daily starting from Day -6 until disease progression.
Pemetrexed 500 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first. | 72 |
| Pemetrexed/Carboplatin Pemetrexed 500 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first. | 74 |
| Docetaxel/Carboplatin Docetaxel 75 mg/m\^2 and carboplatin AUC 6 mg\*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first. | 72 |
| Total | 218 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 9 | 9 | 13 |
| Overall Study | Death | 1 | 0 | 1 |
| Overall Study | Disease Progression | 47 | 24 | 28 |
| Overall Study | New Primary Disease Identified | 1 | 1 | 0 |
| Overall Study | Physician Decision | 3 | 4 | 3 |
| Overall Study | Protocol Violation | 1 | 0 | 0 |
| Overall Study | Sponsor Decision | 1 | 0 | 0 |
| Overall Study | Unrelated Complication | 3 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 2 | 3 |
Baseline characteristics
| Characteristic | Enzastaurin/Pemetrexed/Carboplatin | Pemetrexed/Carboplatin | Docetaxel/Carboplatin | Total |
|---|---|---|---|---|
| Age, Continuous | 65.2 years STANDARD_DEVIATION 9.8 | 64.0 years STANDARD_DEVIATION 10 | 64.0 years STANDARD_DEVIATION 9.1 | 64.4 years STANDARD_DEVIATION 9.8 |
| Disease Stage at Study Entry Stage IIIB | 6 Participants | 5 Participants | 6 Participants | 17 Participants |
| Disease Stage at Study Entry Stage IV | 66 Participants | 69 Participants | 66 Participants | 201 Participants |
| Race/Ethnicity, Customized African | 5 Participants | 11 Participants | 8 Participants | 24 Participants |
| Race/Ethnicity, Customized Caucasian | 62 Participants | 63 Participants | 63 Participants | 188 Participants |
| Race/Ethnicity, Customized Hispanic | 5 Participants | 0 Participants | 1 Participants | 6 Participants |
| Region of Enrollment United States | 72 Participants | 74 Participants | 72 Participants | 218 Participants |
| Sex: Female, Male Female | 31 Participants | 33 Participants | 30 Participants | 94 Participants |
| Sex: Female, Male Male | 41 Participants | 41 Participants | 42 Participants | 124 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 63 / 67 | 70 / 72 | 69 / 70 |
| serious Total, serious adverse events | 35 / 67 | 20 / 72 | 26 / 70 |
Outcome results
Primary
Time to Disease Progression
Time to disease progression was defined as the time from randomization to the first date of documented disease progression or death if the participant dies due to disease progression. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. Progressive disease (PD) was defined as having at least a 20% increase in sum of the longest diameter of target lesions. For participants who have not had documented disease progression, time to disease progression was censored at the date of death or date of last visit. For participants who received other anti-tumor therapy prior to disease progression, time to disease progression was censored at the first available date of other anti-tumor therapy.
Time frame: Baseline to measured PD up to 22.3 months
Population: All randomized participants. Twenty (20) participants in Enzastaurin/Pemetrexed/Carboplatin group, 15 participants in Pemetrexed/Carboplatin group, and 17 participants in Docetaxel/Carboplatin group were censored for analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enzastaurin/Pemetrexed/Carboplatin | Time to Disease Progression | 4.6 months |
| Pemetrexed/Carboplatin | Time to Disease Progression | 6.0 months |
| Docetaxel/Carboplatin | Time to Disease Progression | 4.1 months |
p-value: 0.4Log Rank
p-value: 0.19Log Rank
Secondary
Assessment of Smoking History (All Participants) and Hormone Replacement Therapy (Female Participants Only) Associated With Clinical Outcomes
Data for smoking history and hormone replacement therapy were collected but were not intended to be analyzed at the individual study level.
Time frame: Baseline
Population: Zero participants were analyzed due to insufficient samples being collected.
Secondary
Change From Baseline in Total Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale
The FACT-L version 4 scale is used to assess health-related quality of life (HRQoL) in participants with lung cancer. The FACT-L has 5 subscales: Physical Well-Being (PWB), Social and Family Well-Being (SFWB) and Functional Well-Being (FWB) subscales which include 7 items each, Emotional Well-Being (EWB) subscale which includes 6 items, and a Lung-Cancer Specific (LCS) subscale which include 7 items. Total FACT-L is the sum of all 5 subscales. Each item is scored from 0 to 4 giving a total overall score from 0 equal to worst quality of life to 136 equal to best quality of life. The Least Square (LS) mean was calculated using an analysis of covariance (ANCOVA) model adjusted for change scores and baseline scores.
Time frame: Baseline, Cycle 1 (Week 3), Cycle 2 (Week 6), Cycle 3 (Week 9), Cycle 4 (Week 12), Cycle 5 (Week 15) and Cycle 6 (Week 18) [21-day cycle each]
Population: Randomized participants with non-missing FACT-L data both at baseline and at the specified cycle.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Enzastaurin/Pemetrexed/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale | Cycle 1 (Week 3) | -3.98 units on a scale | Standard Error 1.86 |
| Enzastaurin/Pemetrexed/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale | Cycle 2 (Week 6) | -3.25 units on a scale | Standard Error 2.19 |
| Enzastaurin/Pemetrexed/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale | Cycle 3 (Week 9) | 0.39 units on a scale | Standard Error 2.3 |
| Enzastaurin/Pemetrexed/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale | Cycle 4 (Week 12) | 0.31 units on a scale | Standard Error 2.47 |
| Enzastaurin/Pemetrexed/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale | Cycle 5 (Week 15) | 1.89 units on a scale | Standard Error 2.95 |
| Enzastaurin/Pemetrexed/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale | Cycle 6 (Week 18) | 7.38 units on a scale | Standard Error 3.54 |
| Pemetrexed/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale | Cycle 6 (Week 18) | -0.83 units on a scale | Standard Error 2.84 |
| Pemetrexed/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale | Cycle 1 (Week 3) | 1.12 units on a scale | Standard Error 1.78 |
| Pemetrexed/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale | Cycle 4 (Week 12) | 3.54 units on a scale | Standard Error 2.23 |
| Pemetrexed/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale | Cycle 5 (Week 15) | -0.26 units on a scale | Standard Error 2.57 |
| Pemetrexed/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale | Cycle 2 (Week 6) | -1.54 units on a scale | Standard Error 2.08 |
| Pemetrexed/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale | Cycle 3 (Week 9) | 0.64 units on a scale | Standard Error 2.25 |
| Docetaxel/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale | Cycle 2 (Week 6) | -2.16 units on a scale | Standard Error 2.42 |
| Docetaxel/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale | Cycle 3 (Week 9) | -1.93 units on a scale | Standard Error 2.49 |
| Docetaxel/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale | Cycle 6 (Week 18) | 3.38 units on a scale | Standard Error 3.54 |
| Docetaxel/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale | Cycle 4 (Week 12) | -0.81 units on a scale | Standard Error 2.5 |
| Docetaxel/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale | Cycle 1 (Week 3) | -3.33 units on a scale | Standard Error 1.88 |
| Docetaxel/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale | Cycle 5 (Week 15) | -4.69 units on a scale | Standard Error 2.79 |
p-value: 0.96ANCOVA
p-value: 0.15ANCOVA
p-value: 0.92ANCOVA
p-value: 0.97ANCOVA
p-value: 0.71ANCOVA
p-value: 0.66ANCOVA
p-value: 0.93ANCOVA
p-value: 0.33ANCOVA
p-value: 0.19ANCOVA
p-value: 0.4ANCOVA
p-value: 0.63ANCOVA
p-value: 0.55ANCOVA
Secondary
Change From Baseline in Total Functional Assessment of Cancer Therapy -Taxane (FACT-Taxane) Scale
The FACT-Taxane version 4 scale is used to assess HRQoL in participants receiving taxane chemotherapy. The FACT-taxane has 5 subscales: PWB, SFWB, and FWB subscales which include 7 items each, EWB subscale which includes 6 items, and a taxane subscale which include 16 items and has two domains (neurotoxicity and taxane). Total FACT-Taxane is the sum of all the 5 subscales. Each item is scored from 0 to 4 giving a total overall score from 0 worst quality of life to 172 best quality of life. The LS mean was calculated using an ANCOVA model adjusted for change scores and baseline scores.
Time frame: Baseline, Cycle 1 (Week 3), Cycle 2 (Week 6), Cycle 3 (Week 9), Cycle 4 (Week 12), Cycle 5 (Week 15) and Cycle 6 (Week 18) [21-day cycle each]
Population: Randomized participants with non-missing FACT-Taxane data both at baseline and at the specified cycle.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Enzastaurin/Pemetrexed/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy -Taxane (FACT-Taxane) Scale | Cycle 1 (Week 3) | -3.16 units on a scale | Standard Error 2.2 |
| Enzastaurin/Pemetrexed/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy -Taxane (FACT-Taxane) Scale | Cycle 2 (Week 6) | -6.22 units on a scale | Standard Error 2.9 |
| Enzastaurin/Pemetrexed/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy -Taxane (FACT-Taxane) Scale | Cycle 3 (Week 9) | -1.89 units on a scale | Standard Error 3.35 |
| Enzastaurin/Pemetrexed/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy -Taxane (FACT-Taxane) Scale | Cycle 4 (Week 12) | -2.28 units on a scale | Standard Error 3.65 |
| Enzastaurin/Pemetrexed/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy -Taxane (FACT-Taxane) Scale | Cycle 5 (Week 15) | -2.52 units on a scale | Standard Error 3.71 |
| Enzastaurin/Pemetrexed/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy -Taxane (FACT-Taxane) Scale | Cycle 6 (Week 18) | 2.77 units on a scale | Standard Error 3.93 |
| Pemetrexed/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy -Taxane (FACT-Taxane) Scale | Cycle 6 (Week 18) | -2.81 units on a scale | Standard Error 3.26 |
| Pemetrexed/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy -Taxane (FACT-Taxane) Scale | Cycle 1 (Week 3) | -0.78 units on a scale | Standard Error 2.08 |
| Pemetrexed/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy -Taxane (FACT-Taxane) Scale | Cycle 4 (Week 12) | -0.77 units on a scale | Standard Error 3.29 |
| Pemetrexed/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy -Taxane (FACT-Taxane) Scale | Cycle 5 (Week 15) | -3.11 units on a scale | Standard Error 3.24 |
| Pemetrexed/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy -Taxane (FACT-Taxane) Scale | Cycle 2 (Week 6) | -5.66 units on a scale | Standard Error 2.76 |
| Pemetrexed/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy -Taxane (FACT-Taxane) Scale | Cycle 3 (Week 9) | -1.52 units on a scale | Standard Error 3.32 |
| Docetaxel/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy -Taxane (FACT-Taxane) Scale | Cycle 2 (Week 6) | -3.13 units on a scale | Standard Error 3.16 |
| Docetaxel/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy -Taxane (FACT-Taxane) Scale | Cycle 3 (Week 9) | -4.40 units on a scale | Standard Error 3.62 |
| Docetaxel/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy -Taxane (FACT-Taxane) Scale | Cycle 6 (Week 18) | -0.34 units on a scale | Standard Error 4.06 |
| Docetaxel/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy -Taxane (FACT-Taxane) Scale | Cycle 4 (Week 12) | -2.58 units on a scale | Standard Error 3.74 |
| Docetaxel/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy -Taxane (FACT-Taxane) Scale | Cycle 1 (Week 3) | -2.17 units on a scale | Standard Error 2.2 |
| Docetaxel/Carboplatin | Change From Baseline in Total Functional Assessment of Cancer Therapy -Taxane (FACT-Taxane) Scale | Cycle 5 (Week 15) | -7.74 units on a scale | Standard Error 3.51 |
p-value: 0.93ANCOVA
p-value: 0.86ANCOVA
p-value: 0.69ANCOVA
p-value: 0.77ANCOVA
p-value: 0.83ANCOVA
p-value: 0.78ANCOVA
p-value: 1ANCOVA
p-value: 0.91ANCOVA
p-value: 0.49ANCOVA
p-value: 0.53ANCOVA
p-value: 0.8ANCOVA
p-value: 0.85ANCOVA
Secondary
Duration of CR or PR (Duration of Response)
The duration of a CR or PR was defined as the time from first objective status assessment of CR or PR to the first time of progression or death due to any cause. Response was defined using RECIST, version 1.0 criteria. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions.
Time frame: Date of first response to the date of progression or death due to any cause up to 22.3 months
Population: All randomized participants. 63 participants in Enzastaurin/Pemetrexed/Carboplatin group, 58 participants in Pemetrexed/Carboplatin group, and 53 participants in Docetaxel/Carboplatin group were censored for analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enzastaurin/Pemetrexed/Carboplatin | Duration of CR or PR (Duration of Response) | 7.4 months |
| Pemetrexed/Carboplatin | Duration of CR or PR (Duration of Response) | 9.3 months |
| Docetaxel/Carboplatin | Duration of CR or PR (Duration of Response) | 5.8 months |
Secondary
Number of Participants With Adverse Events (AEs) or Deaths
Data presented are the number of participants who experienced 1 or more AEs or any serious AEs (SAEs) regardless of causality, or deaths during the study including 30 days after treatment discontinuation. A summary of SAEs and other non-serious AEs is located in the Reported Adverse Events section of this report.
Time frame: Baseline through study completion up to 6 cycles (21-day cycle each) and 30-day safety follow-up
Population: Randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Enzastaurin/Pemetrexed/Carboplatin | Number of Participants With Adverse Events (AEs) or Deaths | SAEs | 35 Participants |
| Enzastaurin/Pemetrexed/Carboplatin | Number of Participants With Adverse Events (AEs) or Deaths | AEs | 63 Participants |
| Enzastaurin/Pemetrexed/Carboplatin | Number of Participants With Adverse Events (AEs) or Deaths | Deaths Due to AEs | 3 Participants |
| Pemetrexed/Carboplatin | Number of Participants With Adverse Events (AEs) or Deaths | SAEs | 20 Participants |
| Pemetrexed/Carboplatin | Number of Participants With Adverse Events (AEs) or Deaths | AEs | 70 Participants |
| Pemetrexed/Carboplatin | Number of Participants With Adverse Events (AEs) or Deaths | Deaths Due to AEs | 5 Participants |
| Docetaxel/Carboplatin | Number of Participants With Adverse Events (AEs) or Deaths | AEs | 69 Participants |
| Docetaxel/Carboplatin | Number of Participants With Adverse Events (AEs) or Deaths | Deaths Due to AEs | 4 Participants |
| Docetaxel/Carboplatin | Number of Participants With Adverse Events (AEs) or Deaths | SAEs | 26 Participants |
Secondary
Number of Participants With Complete Response (CR) or Partial Response (PR) [Tumor Response]
Response was defined using RECIST, version 1.0 criteria. Participants with a best response of CR or PR were considered to have had a tumor response. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions.
Time frame: Baseline to measured PD up to 22.3 months
Population: All randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Enzastaurin/Pemetrexed/Carboplatin | Number of Participants With Complete Response (CR) or Partial Response (PR) [Tumor Response] | 9 Participants |
| Pemetrexed/Carboplatin | Number of Participants With Complete Response (CR) or Partial Response (PR) [Tumor Response] | 16 Participants |
| Docetaxel/Carboplatin | Number of Participants With Complete Response (CR) or Partial Response (PR) [Tumor Response] | 19 Participants |
Secondary
Overall Survival (OS)
OS was the duration from the date of randomization to the date of death from any cause. For participants who were alive, OS was censored at the date of last follow-up visit or at the date of last contact.
Time frame: Baseline to date of death from any cause up to 35 months
Population: All randomized participants. Sixteen (16) participants in Enzastaurin/Pemetrexed/Carboplatin group, 20 participants in Pemetrexed/Carboplatin group, and 19 participants in Docetaxel/Carboplatin group were censored for analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enzastaurin/Pemetrexed/Carboplatin | Overall Survival (OS) | 7.2 months |
| Pemetrexed/Carboplatin | Overall Survival (OS) | 12.7 months |
| Docetaxel/Carboplatin | Overall Survival (OS) | 9.2 months |
p-value: 0.87Log Rank
p-value: 0.05Log Rank
Secondary
Time-to-Treatment Failure (TTF)
TTF was defined as the time from randomization to the first observation of PD, death due to any cause, or early discontinuation of treatment. Response was defined using RECIST, version 1.0 criteria. PD was defined as having at least a 20% increase in sum of longest diameter of target lesions. TTF was censored at the date of the last follow-up visit for participants who did not discontinue early, who were still alive, and who have not progressed.
Time frame: Baseline to stopping treatment up to 14.1 months
Population: All randomized participants. Thirty four (34) participants in Pemetrexed/Carboplatin group and 23 participants in Docetaxel/Carboplatin group were censored for analysis. No participants were censored in Enzastaurin/Pemetrexed/Carboplatin group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enzastaurin/Pemetrexed/Carboplatin | Time-to-Treatment Failure (TTF) | 2.6 months |
| Pemetrexed/Carboplatin | Time-to-Treatment Failure (TTF) | 3.8 months |
| Docetaxel/Carboplatin | Time-to-Treatment Failure (TTF) | 2.6 months |
p-value: 0.71Log Rank
p-value: 0.04Log Rank
Secondary
Tumor Biomarkers Associated With Clinical Outcomes
As specified in the protocol, tumor biomarker samples were collected from participants on the pemetrexed arms only but were not intended to be analyzed at the individual study level.
Time frame: Baseline, Cycle 1, Cycle 2 (21-day cycle each), and 30-day post study treatment follow-up
Population: Zero participants were analyzed due to insufficient samples being collected.